The purpose of this proposed project is to further define the dimensions of extraglandular estrogen production. Specifically, it is the purpose of this project to ascertain the physiologic and pathophysiologic role of estrogen produced at sites other than the adrenal, ovary, testis, or placenta. Previous studies have shown that extraglandular estrogen production from utilization of circulating C19 precursors (androstenedione and testosterone) occupy a key role in a consideration of estrogen production in man. Further, preliminary studies have shown that this is not necessarily a static process, but rather is influenced by total body metabolic events such that alterations in estrogen production at extraglandular sites may obtain in the face of aging, obesity, and liver disease. In addition, increased availability of substrate (androstenedione and testosterone) may also result in increased extraglandular estrogen production. It has also been determined that during childhood there is a marked reduction in peripheral aromatase activity such that from birth until the just prepubertal period there is a 70-fold decrease in the extent of peripheral aromatization of plasma C19 steroids per pound of body weight. This proposal, therefore, addresses itself to a further definition of the dimensions of extraglandular estrogen production as these mechanisms may participate in physiologic and pathophysiologic processes.